Inhibition of tumor progression by suppression of stress protein GRP78/BiP induction in fibrosarcoma B/C10ME
Inhibition of tumor progression by suppression of stress protein GRP78/BiP induction in fibrosarcoma B/C10ME
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DOI：
10.1073/pnas.93.15.7690
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发表时间：
1996-07-23
影响因子：
11.1
通讯作者：
Lee, AS
中科院分区：
文献类型：
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作者：
Jamora, C;Dennert, G;Lee, AS
应激蛋白GRP 78/BiP在进行性生长的肿瘤中被高度诱导，最近已经显示出在体外对细胞毒性T细胞和肿瘤坏死因子的溶解发挥保护作用。这就提出了一个问题，是否在体外观察到的保护功能的GRP 78/BiP转化为在体内的情况下，肿瘤的生长进行性，杀死主机，在此我们报告的分子抑制GRP 78/BiP诱导纤维肉瘤B/C10 ME，而不影响体外细胞增殖，导致凋亡细胞死亡后Ca 2+耗尽内质网的急剧增加。当将不能诱导GRP 78/BiP的B/C10 ME细胞注射到小鼠中时，最初形成肿瘤，然而，可能由于细胞毒性T细胞应答而消退，所述细胞毒性T细胞应答可通过用消退小鼠的脾细胞对肿瘤的强体外应答来证明。由于对细胞凋亡的敏感性是肿瘤排斥的关键，这些结果可能为通过调节应激蛋白GRP 78/BiP治疗癌症指明了新的途径。
Stress protein GRP78/BiP is highly induced in progressively growing tumors acid has recently been shown to exert a protective role against lysis by cytotoxic T cells and tumor necrosis factor in vitro. This raises the question whether the in vitro observed protective function of GRP78/BiP translates into the in vivo situation in which tumors grow progressively , killing the host, Herein we report that molecular inhibition of GRP78/BiP induction in the fibrosarcoma B/C10ME, while not affecting in vitro cell proliferation, causes a dramatic increase in apoptotic cell death upon Ca2+ depletion of the endoplasmic reticulum. When B/C10ME cells incapable of inducing GRP78/BiP are injected into mice, tumors are initially formed that, however, regress presumably due to a cytotoxic T-cell response demonstrable by a strong in vitro response to the tumor with spleen cells of regressor mice, Since sensitivity to apoptosis is key to tumor rejection, these results may point to new approaches to the therapy of cancer via regulation of stress protein GRP78/BiP.